Effect of tolbutamide on myocardial metabolism and mechanical performance of the diabetic rat.

Abstract:

:Exposure of the isolated, glucose-perfused rat heart to buffer containing 0.4 mM tolbutamide resulted in significant changes in both energy metabolism and myocardial contractility. In the nondiabetic, tolbutamide mediated only small increases in mechanical function at low atrial filling pressure, but this effect increased with increasing preload. By contrast, the stimulation of mechanical function resulting from exposure of the diabetic heart to tolbutamide was independent of preload. As a result, the tolbutamide-mediated, positive inotropic effect in the diabetic heart was greater at lower, but not higher, preload values than the effect in the nondiabetic. Moreover, the changes in energy metabolism initiated by tolbutamide were considerably larger in the diabetic. The most prominent effect was the mobilization of glycogen by tolbutamide in the diabetic, which was considerably greater than that observed in the nondiabetic. The drug also enhanced glucose utilization. The net effect of sulfonylurea exposure was to shift from preferential use of fatty acids as an energy source for contraction to use of glucose. Since the most prominent effect of the drug in the diabetic was the stimulation of glycogenolysis, it is concluded that tolbutamide can dramatically alter the metabolism of a tissue without acting through insulin.

journal_name

Diabetes

journal_title

Diabetes

authors

Tan BH,Wilson GL,Schaffer SW

doi

10.2337/diab.33.12.1138

subject

Has Abstract

pub_date

1984-12-01 00:00:00

pages

1138-43

issue

12

eissn

0012-1797

issn

1939-327X

journal_volume

33

pub_type

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